Role of CD45 signaling pathway in galactoxylomannan-induced T cell damage

Eva Pericolini, Elena Gabrielli, Giovanni Bistoni, Elio Cenci, Stefano Perito, Siu Kei Chow, Francesca Riuzzi, Rosario Donato, Arturo Casadevall, Anna Vecchiarelli

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Abstract

Previously, we reported that Galactoxylomannan (GalXM) activates the extrinsic and intrinsic apoptotic pathways through an interaction with the glycoreceptors on T cells. In this study we establish the role of the glycoreceptor CD45 in GalXM-induced T cell apoptosis, using CD45+/+ and CD45-/- cell lines, derived from BW5147 murine T cell lymphoma. Our results show that whereas CD45 expression is not required for GalXM association by the cells, it is essential for apoptosis induction. In CD45+/+ cells, CD45 triggering by GalXM reduces the activation of Lck, ZAP70 and Erk1/2. Conversely, in CD45-/- cells, Lck was hyperphosphorylated and did not show any modulation after GalXM stimulation. On the whole, our findings provide evidence that the negative regulation of Lck activation occurs via CD45 engagement. This appears to be related to the capacity of GalXM to antagonize T cell activation and induce T cell death. Overall this mechanism may be responsible for the immune paralysis that follows GalXM administration and could explain the powerful immunosuppression that accompanies cryptococcosis.

Original languageEnglish (US)
Article numbere12720
Pages (from-to)1-13
Number of pages13
JournalPloS one
Volume5
Issue number9
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Pericolini, E., Gabrielli, E., Bistoni, G., Cenci, E., Perito, S., Chow, S. K., Riuzzi, F., Donato, R., Casadevall, A., & Vecchiarelli, A. (2010). Role of CD45 signaling pathway in galactoxylomannan-induced T cell damage. PloS one, 5(9), 1-13. [e12720]. https://doi.org/10.1371/journal.pone.0012720